title: A systems level predictive model for global gene regulation of methanogenesis in a hydrogenotrophic methanogen.
abstract: Methanogens catalyze the critical methane-producing step (called methanogenesis) in the anaerobic decomposition of organic matter. Here, we present the first predictive model of global gene regulation of methanogenesis in a hydrogenotrophic methanogen, Methanococcus maripaludis. We generated a comprehensive list of genes (protein-coding and noncoding) for M. maripaludis through integrated analysis of the transcriptome structure and a newly constructed Peptide Atlas. The environment and gene-regulatory influence network (EGRIN) model of the strain was constructed from a compendium of transcriptome data that was collected over 58 different steady-state and time-course experiments that were performed in chemostats or batch cultures under a spectrum of environmental perturbations that modulated methanogenesis. Analyses of the EGRIN model have revealed novel components of methanogenesis that included at least three additional protein-coding genes of previously unknown function as well as one noncoding RNA. We discovered that at least five regulatory mechanisms act in a combinatorial scheme to intercoordinate key steps of methanogenesis with different processes such as motility, ATP biosynthesis, and carbon assimilation. Through a combination of genetic and environmental perturbation experiments we have validated the EGRIN-predicted role of two novel transcription factors in the regulation of phosphate-dependent repression of formate dehydrogenase-a key enzyme in the methanogenesis pathway. The EGRIN model demonstrates regulatory affiliations within methanogenesis as well as between methanogenesis and other cellular functions.
authors.affiliation: Institute for Systems Biology, Seattle, Washington 98109, USA;
authors.forename: Sung Ho
authors.initials: SH
authors.lastname: Yoon
authors.forename: Serdar
authors.initials: S
authors.lastname: Turkarslan
authors.forename: David J
authors.initials: DJ
authors.lastname: Reiss
authors.forename: Min
authors.initials: M
authors.lastname: Pan
authors.forename: June A
authors.initials: JA
authors.lastname: Burn
authors.forename: Kyle C
authors.initials: KC
authors.lastname: Costa
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Lie
authors.forename: Joseph
authors.initials: J
authors.lastname: Slagel
authors.forename: Robert L
authors.initials: RL
authors.lastname: Moritz
authors.forename: Murray
authors.initials: M
authors.lastname: Hackett
authors.forename: John A
authors.initials: JA
authors.lastname: Leigh
authors.forename: Nitin S
authors.initials: NS
authors.lastname: Baliga
mesh_terms: D019843:Archaeal Proteins / Q000235:genetics / Q000378:metabolism; D005560:Formate Dehydrogenases / Q000235:genetics; D020869:Gene Expression Profiling; D019848:Gene Expression Regulation, Archaeal; D059647:Gene-Environment Interaction; D019766:Genes, Archaeal; D006859:Hydrogen / Q000378:metabolism; D053858:Metabolic Networks and Pathways / Q000235:genetics*; D008697:Methane / Q000096:biosynthesis*; D017017:Methanococcus / Q000201:enzymology* / Q000235:genetics* / Q000378:metabolism; D008957:Models, Genetic; D017384:Sequence Deletion
chemical_list: D019843:Archaeal Proteins; D006859:Hydrogen; D005560:Formate Dehydrogenases; D008697:Methane